IFC-305, an adenosine derivative, inhibits the osteolytic metastases of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of cancer characterized by limited therapeutic options and a propensity to form metastasis, particularly to bone. Given the mortality and morbidity linked to TNBC, the advancement of novel and effective therapies is essential. This work studies the potential of an adenosine derivative compound (IFC-305) as a therapeutic agent for breast cancer bone metastasis. It focuses on its effects on bone metastasis, including cell viability, migration, cell cycle, and apoptosis in vitro. In vitro assays demonstrated that IFC-305 significantly reduced TNBC cell viability and migration in a dose-dependent manner. Additionally, it promoted cell cycle arrest and decreased the proportion of cells in the S phase, although it did not induce apoptosis in 4T1 cells. Furthermore, in vivo experiments using a murine model of bone metastasis revealed that treatment with IFC-305 attenuated osteolytic lesions associated with breast cancer metastasis. Importantly, our findings highlight an interaction between this adenosine derivative and the TGF-β signaling pathway. The derivative compound effectively inhibited SMAD2/3 phosphorylation, a key mediator of TGF-β signaling pathway involved in cell growth, differentiation, migration and metastatic progression. Besides, IFC-305 reduced TGF-β regulated PMPEA1 expression, a gene associated with cancer stemness and tumor invasion. These findings provide evidence for the therapeutic potential of the IFC-305 in treating metastatic breast cancer in the bone and warrant further investigation to fully elucidate its mechanism of action and evaluate its clinical translatability.